RT Journal Article SR Electronic T1 Quantitative Structure–Cytotoxicity Relationship of Pyrano[4,3-b]chromones JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 4449 OP 4457 DO 10.21873/anticanres.12747 VO 38 IS 8 A1 JUNKO NAGAI A1 HAIXIA SHI A1 YUKA KUBOTA A1 KENJIRO BANDOW A1 NORIYUKI OKUDAIRA A1 YOSHIHIRO UESAWA A1 HIROSHI SAKAGAMI A1 MINEKO TOMOMURA A1 AKITO TOMOMURA A1 KOICHI TAKAO A1 YOSHIAKI SUGITA YR 2018 UL http://ar.iiarjournals.org/content/38/8/4449.abstract AB Background/Aim: 4H-1-Benzopyran-4-one (chromone) provides a backbone structure for the chemical synthesis of potent anticancer drugs. Since studies of the biological activity of pyrano[4,3-b]chromones are limited, we investigated a total of 20 pyrano[4,3-b]chromones (10 sets of diastereomers) for their cytotoxicity against four human oral squamous cell carcinoma (OSCC) cell lines and human normal oral cells, and then carried out a quantitative structure–activity relationship (QSAR) analysis. Materials and Methods: Cytotoxicity was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Tumor-specificity (TS) was evaluated by the ratio of mean 50% cytotoxic concentration (CC50) against normal oral cells to that against human OSCC cell lines. Potency-selectivity expression (PSE) value was calculated by dividing the TS value by the CC50 against tumor cells. Apoptosis induction was evaluated by morphological observation, western blot analysis and cell-cycle analysis. For QSAR analysis, a total of 3,072 physicochemical, structural and quantum chemical features were calculated from the most stabilized structure optimized using CORINA. Results: 8-Chloro-4,4a-dihydro-3-methoxy-3-methyl-3H,10H-pyrano[4,3-b][1]benzopyran-10-one (16) and 3-ethoxy-4,4a-dihydro-8-methoxy-3H,10H-pyrano[4,3-b][1]benzopyran-10-one (17) had the highest TS, higher than that of 5-flurouracil and melphalan, without induction of apoptosis. Compound 16 induced cytostatic growth inhibition and much lower cytotoxicity against human normal oral keratinocytes compared to doxorubicin. TS of 20 pyrano[4,3-b]chromones was correlated with 3D structure, polarity, ionic potential and electric state. Conclusion: Chemical modification of 16 may be a potential choice for designing a new type of anticancer drug.